-
外観
白色～うすい褐色, 結晶性粉末～粉末
-
溶解性
水に溶ける。
-
用途
DNA ポリメラーゼ及び RNA
ポリメラーゼを阻害し、DNA/RNA 合成阻害
作用を示します。
-
効能
抗悪性腫瘍薬, 代謝拮抗薬
-
商品名
フルダラ (サノフィ); フルダラ (サノフィ)
-
使用上の注意
不活性ガス封入
-
説明
Fludarabine phosphate is an antimetabolite indicated for the treatment of B cell
lymphocytic leukemia. It is reportedly effective in patients refractory to other
therapies. Fludarabine phosphate acts by inhibiting primer RNA synthesis. Its side
effects include bone marrow suppression, anemia, thrombocytopenia and neutropenia.
-
化学的特性
White or almost white, crystalline powder, hygroscopic.
-
使用
Fludarabine phosphate is used for the treatment of chronic lymphatic leukemia and low-grade lymphoma. In the circulation,fludarabine phosphate is immediately dephosphorylated to the nucleoside fludarabine. About 30-40% of nucleoside fludarabine is excreted into the urine. In addition, fludarabine is metabolized into a hypoxanthine metabolite also excreted in the urine.Intracellularly,fludarabine is stepwise rephosphorylated to the active triphosphate. Deoxycytidine kinase is the dominant, if not the exclusive,enzyme for the formation of the monophosphate. Adenylate kinase and nucleoside diphosphate kinase are believed to be involved in the formation of the diphosphate and triphosphate,respectively.
-
定義
ChEBI: Fludarabine phosphate is a purine arabinonucleoside monophosphate having 2-fluoroadenine as the nucleobase. A prodrug, it is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. Once incorporated into DNA, 2-fluoro-ara-ATP functions as a DNA chain terminator. It is used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to, or whose disease has progressed during, treatment with at least one standard alkylating-agent containing regimenas. It has a role as an antimetabolite, an antineoplastic agent, an immunosuppressive agent, an antiviral agent, a prodrug and a DNA synthesis inhibitor. It is an organofluorine compound, a nucleoside analogue and a purine arabinonucleoside monophosphate. It derives from a 2-fluoroadenine.
-
薬理学
Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Phase I studies in humans have demonstrated that fludarabine phosphate is rapidly converted to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous infusion.
Consequently, clinical pharmacology studies have focused on 2-fluoro-ara-A pharmacokinetics. After the five daily doses of 25 mg 2-fluoro-ara-AMP/m2 to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation. During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours. In vitro, plasma protein binding of fludarabine ranged between 19% and 29%.
-
臨床応用
Fludarabine phosphate (Fludara ® ), is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine(ara-A), which differs only by the presence of a fluorine atom at position 2 of the purine moiety and a phosphate group at position 5 of the arabinose moiety (Plunkett et al., 1993). These structural modifications result in increased aqueous solubility and resistance to enzymatic degradation by adenosine deaminases compared to vidarabine (Brockman et al., 1977; Plunkett et al., 1990). Fludarabine phosphate is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating agent containing regimen (Boogaerts et al., 2001; Rossi et al., 2004).
